Benzo(1,5)diazocinones

ABSTRACT

THE INVENTION DISCLOSES COMPOUNDS OF THE CLASS OF 6PHENYL-3,4-DIHYDRO (1,5) BENZODIAZOCIN-2-(1H)-ONES USEFUL AS TRANQUILIZERS. ALSO DISCLOSED IS PREPARATION OF SAID COMPOUNDS FEATURING INTERMEDIATES WHICH ARE 1,5-METHANO1,5-BENZODIAZOCIN-2-ONES WHICH ARE CONVERTED BY ACID TREATMENT TO THE CORRESPONDING 6-PHENYL-3,4,5,6-TETRAHYDRO (1,5) BENZODIAZOCIN-2(1H)-ONES WHICH IN TURN MAY BE OXIDIZED TO OBTAIN THE FIRST-MENTIONED CLASS OF COMPOUNDS.

United States Patent 3,577,557 BENZO[1,5]DIAZOCINONES Hans Ott, ConventStation, N.J., assiguor t0 Sandoz-Wander, Inc., Hanover, NJ. No Drawing.Filed Dec. 9, 1966, Ser. No. 600,403 Int. Cl. C07d 53/00, 51/48 U.S. Cl.260239.3 20 Claims ABSTRACT OF THE DISCLOSURE This invention relates tonovel bicyclic compounds. In particular, the invention pertains to6-phenyl-3,4-dihydro[1,5]benzodiazocinones and methods for preparing thesame. The invention further relates to intermediates which are useful inpreparing the above compounds and processes for preparing saidintermediates.

The 3,4-dihydro[1,5]benzodiazocinones of the present invention may berepresented structurally as follows:

wherein X represents hydrogen; chloro; bromo; nitro or trifluoromethyl;and

R represents hydrogen; lower alkyl, preferably containing from 1 to 4carbon atoms, e.g., methyl, ethyl, propyl and butyl; ordi(lower)alkylamino(lower)alkyl, each of the alkyl substituents beingthe same or different and preferably containing from 1 to 4 carbonatoms, e.g., dimethylaminomethyl, p-dimethylaminoethyl,'ydimethylaminopropyl, N-methyl-N-ethylaminoethyl and"y-dlthYlflIIllIlOPfOPYl.

The above compounds are prepared by treating a 6-phenyl-1,3,4,5-tetrahydro-6H-1,5 methano 1,5-benzodiazocin-Z-one with anacid to form the corresponding 6- phenyl-3,4,5,6tetrahydro[1,5]benzodiazocin 2-(1H)- one, reacting the latter with anappropriate alkylating agent where substitution at the 1-position isdesired and then oxidizing the resulting l-unsubstituted orl-substituted derivative. The preparation of the l-substituted derivative can also be accomplished by first oxidizing the 6-phenyl-3,4,5,6-tetrahydro[1,5 1benzodiazocin 2(lH)-one to form thecorresponding 6-phenyl-3,4-dihydro[1,5] benzodiazocine-1-(1H)-one andthen treating the latter with an appropriate alkylating agent. Theseprocesses are illustrated by the following Reaction Scheme:

3,577,557 Patented May 4, 1971 "Ice REACTION SCHEME I l? N-C NC H+ e "w1 X D II III Oxidation Alkylatlon Step 3 Step2 O R O H I! I ll N-C /N-CX j X Ia IV Alkylation Oxidation Step2 Step R O a. t fl X Wherein X isas previously defined, and R is other than hydrogen but is otherwise asdefined above.

Conversion of the bridged benzodiazocinone (II) to the corresponding3,4,5,6 tetrahydrobenzodiazocinone (III), as illustrated by Step 1, isconveniently carried out in strongly acidic aqueous medium and at roomtemperature (20-25 C.). Desirably, the acid concentration is in therange of from about 0.1 Normal to about 2. Normal and preferably is inthe range of from about 0.1 Normal to about 1 Normal. Suitable acidswhich may be employed include the inorganic acids, such as the mineralacids, e.g., hydrochloric acid, sulfuric acid and phosphoric acid, andthe organic acids, e.g., oxalic acid, formic acid and tartaric acid.Where the starting material is insoluble in aqueous acid, a suitablewatermiscible inert organic solvent, e.g., dioxane, can be utilized tosolubilize the same and thereby facilitiate the reaction.

In Step 2 of the process, the tetrahydrobenzodiazocinone (III) ordihydrobenzodiazocinone (Ia) is converted in conventional manner to thel-metallo derivative in a suitable inert organic solvent, e.g.,dimethylformamide, dimethylacetamide, diethylacetamide,dimethylsulfoxide and dioxane, and at room temperature, preferably bytreatment with an alkali metal alkoxide, e.g., sodium methoxide andpotassium ethoxide, or sodium hydride and the resulting alkali metalsalt then treated with an appropriate alkylating agent in conventionalmanner. For the preparation of the 1-alkyl derivatives, on appropriatealkyl halide, preferably the bromide or iodide, e.g., methyl bromide,methyl iodide, ethyl iodide and the like, or a dialkylsulfate, e.g.,dimethylsulfate and the like, is employed as the alkylating agent. Forthe preparation of those compounds which are substituted at the1-position with a di(lower)alkylamino(lower)alkyl substituent thecorresponding halide, preferably the bromide or chloride, e.g.,dimethylaminomethyl chloride, p-dimethylaminoethyl bromide,'y-dimethylaminopropyl 3 chloride and B-(N-methyl-N-ethylamino) ethylchloride, is employed as the alkylating agent.

The reaction of alkali metal salt with the alkylating agent ispreferably carried out in the same solvent employed to prepare thealkali metal salt. However, if desired, the alkali metal salt can beisolated and then treated with the alkylating agent. The reactiontemperature is not critical and will for the most part be dependent uponthe reactivity of the alkylating agent. With the more reactivealkylating agents the reaction can be conveniently carried out at roomtemperature or below (25 C.), whereas with the less reactive alkylatingagents elevated temperatures can be employed to facilitate the reaction.

The oxidation (Step 3) of the tetrahydrobenzodiazocinone, III or IV, isreadily eifected in a suitable inert organic solvent, e.g., dioxane andacetone, and at room temperature and in the presence of permanganateions. Preferably, the oxidation is carried out employing sodium orpotassium permanganate.

The starting compounds employed in Reaction Scheme I are prepared byreacting 4-phenyl-3,4-dihydroquinazoline or an appropriately substitutedderivative thereof with an acrylic acid ester, preferably a lower alkylester, e.g., methyl acrylate and ethyl acrylate, to form thecorresponding 3 (B-carbalkoxyethyl)-4-phenyl,3,4-dihydroquinazoline,converting the latter to the corresponding 3-(}?carboxyethyl)-4-phenyl-3,4-dihydroquinazoline, reducing the latter tothe corresponding B-(B-carboxyethyh- 4-phenyl-1,2,3,4tetrahydroquinazoline and dehydrating the latter. This process may beillustrated as follows:

REACTION SCHEME II j CH2=OHCOOR W NE Step 1 N(CH2)2COOR V VI Step 2 j(OHz)2C0OH I i VII i Reduction Step 3 H N X (CH2)2C O OH VIII ldehydration Step 4 Wherein X is as previously defined and R representsalkyl, desirably lower alkyl containing from 1 to 4 carbon atoms andpreferably methyl or ethyl.

The reaction of the dihydroquinazoline (V) with the acrylic acid estercan be carried out in any suitable inert organic solvent, e.g., dioxane,benzene and toluene, and at elevated temperatures, preferably refluxtemperature. However, the use of a solvent is not necessary since anexcess of the acrylate reactant can be used for this purpose. Various ofthe dihydroquinozalines and acrylic acid esters employed are known andcan be prepared as described in the literature. Such others which maynot be specifically known can be prepared from available materials inanalogous manner.

In Step 2 of the process a 3 (,B-carbalkoxyethyD-4-phenyl-3,4-dihydroquinazoline (V1) is hydrolyzed to the corresponding 3(fl-carboxyethyl)-4-phenyl-3,4-dihydroquinazoline (VII). The hydrolysisis readily carried out in an aqueous inert organic solvent at roomtemperature or elevated temperatures and in the presence of a strongbase. The organic solvent is desirably one which is watermiscible, e.g.,methanol, ethanol, dioxane and tetrahydrofuran, and the base ispreferably an alkali metal hydroxide, e.g., sodium hydroxide, potassiumhydroxide and lithium hydroxide, although other strong bases, such asbarium hydroxide can also be used.

Conversion of the dihydroquinazoline (VII) to the cor respondingtetrahydroquinazoline (VIII) (Step 3) is effected by chemical reductionemploying a borohydride, e.g., sodium borohydride, as the reducingagent. The re duction is conveniently carried out in an inert organicsolvent, e.g., methanol, ethanol, dioxane and tetrahydrofuran, and atroom temperature or elevated temperatures up to reflux temperature.

In the last step of the process (Step 4) the tetrahydroquinazoline(VIII) is converted to the bridged benzodiazocinone (IX) by dehydration.The dehydration can be readily eifected employing dehydrating agentsconventionally used to bring about ring closure, e.g., thionyl chloride,phosphorus pentachloride and the like. However, the preferreddehydrating agents are the lower alkyl halocarbonates, e.g., ethylchlorocarbonate. The dehydration is carried out in an inert organicsolvent, e.g., dioxane methylene chloride and tetrahydrofuran, and atroom temperature, preferably in the presence of a tertiary amine base,e.g., triethylamine and tertiary butylamine.

The compounds of structural Formula I are useful because they possesspharmacological activity in animals. In particular, the compounds arecentral nervous system depressants and can be used as tranquilizers. Forsuch usage the compounds may be combined with a pharmaceuticallyacceptable carrier, and such other adjuvants as may be necessary, andadministered orally in such forms as tablets, capsules, elixirs,suspensions and the like or parenterally in the form of an injectablesolution or suspension. The dosage administered will, of course, varydepending upon the compound employed and the mode of administration.However, in general, satisfactory results are obtained when administeredat a daily dosage of from about 2 milligrams to about 15 milligrams perkilogram of body weight, preferably given in divided doses, 2 to 4 timesa day, or in sustained release form. For both larger mammals and smalldomestic mammals the daily dosage is generally from about milligrams toabout 1000 milligrams and the preferred dosage forms comprise from about50 milligrams to about 500 milligrams of the compound admixed with asolid or liquid pharmaceutical carrier or diluent.

The intermediate compounds of Formulas III and IV also possesspharmacological activity in animals. In particular, such compounds arecentral nervous system depressants and can be employed as tranquilizers.For such usage the compounds may be administered in the same manner andat the same dosages as indicated above for compounds of Formula I.

A representative formulation is a tablet (prepared by standardtabletting techniques) and containing the following ingredients:

Ingredient Parts by weight 8 chloro l methyl 6 phenyl-3,4-dihydro-[1,5]

benzodiazocin-2(1H)-one 50 Tragacanth 2 Lactose 39.5 Corn starch 5Talcum 3 Magnesium stearate 0.5

The following examples show representative compounds encompassed withinthe scope of this invention and the manner in which such compounds areprepared. However, it is to be understood that the examples are forpurposes of illustration only and are not intended as in any waylimiting the scope of the invention which is defined in the appendedclaims.

Example l.8-ch1oro-6-phenyl-3,4-dihydro- [1,5]benzodiazocin-2(1H)-oneStep A: Preparation of 3-(fl-carbethoxyethyl)-6-chloro-4-phenyl-3,4-dihydroquinazoline.-A solution of 3.8 g. of6-chloro-4-phenyl-3,4-dihydroquinazoline in 50 ml. of ethyl acrylate isrefluxed for 4 hours, then evaporated in vacuo and the residuecrystallized from diethyl ether to obtain3-(fl-carbethoxyethyl)-6-chloro 4 phenyl-3,4-dihydroquinazoline, M.P.107108 C.

Step B: Preparation of 3-(fi-carboxyethyl)-6-ch1oro-4-phenyl-3,4-dihydroquinazoline.A solution of 2.75 g. of3-(,8-carbethoxyethyl)-6 chloro 4 phenyl-3,4-dihydroquinazoline in 30ml. of ethanol and 12 ml. of 2 N sodium hydroxide is kept at roomtemperature overnight and then most of the ethanol is removed at roomtemperature in vacuo. To the resulting mixture is added 250 ml. of 2 Nhydrochloric acid and the resulting solution saturated with sodiumchloride and extracted 3 times with 30 ml. (each) of a mixture ofchloroform and methanol (9:1). The organic phase is evaporated and theresidue crystallized from methylene chloride/ethanol (1:4) to obtain3-(B- carboxyethyl)-6-chloro 4-phenyl-3,4-dihydroquinazoline, M.P.166167 C.

Step C: Preparation of 3-(,B-carboxyethyl)-6-chloro-4phenyl-l,2,3,4-tetrahydroquinazline.--To a solution of 29.3 g. of3-(B-carboxyethyl)-6-chloro-4-phenyl-3,4-dihydroquinazoline in 300 ml.of ethanol and 120 ml. of 2 N sodium hydroxide is added 10 g. of sodiumborohydride. The resulting mixture is heated at 60 C. for 1 hour, theexcess borohydride decomposed by the dropwise addition of 2 Nhydrochloric acid until gas evolution ceases and the ethanol thenevaporated oif at 40 C. in vacuo. The resulting mixture is thenneutralized with 2 N hydrochloric acid to a pH of 7 and then extracted 3times with 200 ml. (each) of chloroform. The combined extracts are driedover anhydrous sodium sulfate and then evaporated to dryness in vacuo toobtain3-(fl-carboxyethyD-G-chloro-4-phenyl-l,2,3,4-tetrahydroquinazoline as alight yellow amorphous residue.

Step D: Preparation of 8-chloro-6-phenyll,3,4,5-tetrahydro-6H-l,5-methano 1,5 benzodiazocin-2-one.To a solutionof 17 g. of 3-(fi-carboxyethyl)-6-chloro-4-phenyl1,2,3,4-tetrahydroquinazoline and 14 ml. of triethylamine in 175 ml. ofdry dioxane, at -10 C., is added dropwise over a period of 5-10 minutes,6.5 ml. of ethylchlorocarbonate. The resulting solution is stirred atroom temperature for 30 minutes and then evaporated to dryness in vacuoat 40-50 C. The residue is dissolved in 200 ml. of methylene chlorideand the resulting solution extracted twice with l00 ml. (each) of asaturated sodium bicarbonate solution. The organic phase is dried overanhydrous sodium sulfate and then evaporated and the residuecrystallized from diethyl ether to obtain8-chloro-6-phenyl-1,3,4,5-tetrahydro 6H 1,5 methano1,5-benzodiazocin-2-one, M.P. 169-170 C.

Step E: Preparation of 8 chloro 6 phenyl 3,4,5,6- tetrahydro[l,5]benzodiazocin 2(lH) one.A solution of 13.6 g. of 8 chloro 6 phenyl1,3,4,5 tetrahyhydro 6H 1,5 methano 1,5 benzodiazocin 2 one, 800 ml. ofdioxane, 1100 ml. of water and ml. of 2 N hydrochloric acid is allowedto stand at room temperature for 30 minutes, then made basic by theaddition of 220 ml. of 1 N sodium bicarbonate solution and thenconcentrated in vacuo to remove most of the dioxane. The crystallinematerial which is formed is recovered by filtration and recrystallizedfrom ethyl acetate to obtain 8 chloro 6 phenyl 3,4,5,6 tetrahydro-[l,5]benzodiazocin-2(lH)-one, M.P. 220 C.

Step F: Preparation of 8 chloro 6 phenyl 3,4 -dihydro [1,5]benzodiazocin2( 1H) one.To a solution of 4.5 g. of 8 chloro 6 phenyl 3,4,5,6tetrahydro [l,5]benzodiazocin 2(lH) one in 150 ml. of dry dioxane isadded a solution of 2.0 g. of potassium permanganate in 40 ml. of Water.The reaction mixture is allowed to stand at room temperature for 4hours, then filtered and the filtrate evaporated to dryness in vacuo.The residue is added to a mixture of 100 ml. of methylene chloride and50 ml. of 5% sodium bicarbonate solution. The organic phase isseparated, dried over anhydrous sodium sulfate and evaporated in vacuo.The residue is crystallized from diethyl ether to obtain 8 chloro 6phenyl 3,4 dihydro [l,5]benzodiazocin 2(lH) one, M.P. 164-166 C.

Example 2.8-chloro-1-methyl-6-phenyl-3,4-dihydro-[1,5]benzodiazocin-2(1H)-one CH3 0 I II To a solution of 4.2 g. of 8chloro 6 phenyl 3,4- dihydro [1,5]benzodiazocin 2(lH) one in 150 ml. ofdimethylformamide is added 0.9 g. of sodium methoxide. The resultingmixture is stirred for 10 minutes at room temperature and then cooled to10 C. To the resulting cooled solution is added, within 10 minutes, 3ml. of methyl iodide and the resulting mixture is allowed to stand for15 minutes at 20 C. and then evaporated in vacuo at 60 C. The residue isadded to a mixture of 100 ml. of methylene chloride and 50 ml. of a 5%solution of sodium bicarbonate. The organic phase is separated, driedover anhydrous sodium sulfate and evaporated. The residue iscrystallized from diethyl ether to obtain 8 chloro 1 methyl 6 phenyl 3,4dihydro- [l,5]benzodiazocin-2(lH)-one, M.P. 167l68 C.

Example 3 .8-chloro-l-methyl-6-phenyl-3 ,4,-dihy-dro-[1,5]benzodiazocin-2(1H)-one (alternate method) Step A: Preparation of 8chloro l methyl 6 phenyl 3,4,5,6 tetrahydro [1,5 Jbenzodiazocin 2( 1H)-one.-To a solution of 4.5 g. of 8 chloro 6 phenyl- 3,4,5,6 tetrahydro[1,51benzodiazocin 2(lH) one in ml. of dimethylformamide is added 1.0 g.of sodium methoxide. The resulting mixture is stirred for minutes atroom temperature and then cooled to 10 C. To the resulting solution isadded, within 10 minutes, 1.94 ml. of methyl iodide and the resultingmixture is allowed to stand at 20 C. for minutes and then evaporated invacuo at 60 C. The residue is added to a mixture of 100 ml. of methylenechloride and 50 m1. of a 5% solution of sodium bicarbonate. The organicphase is separated, dried over anhydrous sodium sulfate and evaporated.The residue is crystallized from diethyl ether to obtain 8 chloro 1methyl 6 phenyl 3,4,5,6- tetrahydro [1,5 ]benzodiazocin 2(1H) one, M.P.151- 153 C.

Step B: Preparation of 8 chloro l methyl 6 phenyl 3,4 dihydro[l,5]benzodiazocin 2(1H) one-To a solution of 0.6 g. of 8 chloro 1methyl- 6 phenyl 3,4,5,6 tetrahydro [1,5]benzodiazocin- 2(lH)-one in ml.of dry dioxane is added '5 ml, of an aqueous potassium permanganatesolution (5.27 g./ 100 ml.). The reaction mixture is allowed to stand atroom temperature for 3 hours, then filtered and the filtrate evaporatedto dryness in vacuo. The residue is added to a mixture of 20 ml. ofmethylene chloride and 10 ml. of a saturated solution of sodiumchloride. The organic phase is separated, dried over anhydrous sodiumsulfate and evaporated in vacuo. The residue is crystallized fromdiethyl ether to obtain 8 chloro 1 methyl 6 phenyl- 3,4 dihydro[1,51benzodiazocin 2(1H) one, M.P. 167168 C.

CH3 0 I ll Step A: Preparation of 3 (18 carbethoxyethyl) 4 phenyl 3,4dihydroquinazoline.-A solution of 20 g. of 4 phenyl 3,4dihydroquinazoline in 180 ml. of ethyl acrylate is refluxed for 2 hours,then evaporated in vacuo to obtain 3 (,6 carbethoxyethyl) 4 phenyl-3,4-dihydroquinazoline as an oil.

Step B: Preparation of 3 8 carboxyethyl) 4 phenyl 3,4dihydroquinazoline.-A solution of 29.5 g. of 3 (fl carbethoxyethyl) 4phenyl 3,4 dihydroquinazoline, 400 ml. of ethanol and 250 ml. of 2 Nsodium hydroxide is kept overnight at room temperature and then most ofthe ethanol is removed at room temperature in vacuo. To the resultingmixture is added 250 ml. of 2 N hydrochloric acid and the resultingsolution saturated with sodium chloride and extracted 3 times with 300ml. (each) of a mixture of chloroform and methanol (9:1). The organicphase is evaporated to obtain 3- fi-carboxyethyl-4-phenyl-3,4-dihydroquinazoline.

Step C: Preparation of 3-(B-carboxyethyl)-4-phenyl-1,2,3,4-tetrahydroquinazoline.-To a solution of 28 g. of 3 (Bcarboxyethyl)-4-phenyl-3,4-dihydroquinazoline, 500 ml. of ethanol and130 ml. of 1 N sodium hydroxide is added 10 g. of sodium borohydride.The resulting mix ture is heated at 60 C. for 1 hour, the excessborohydride decomposed by the dropwise addition of 2 N hydrochloric aciduntil gas evolution ceases and the ethanol then evaporated oif at 40 C.in vacuo. The resulting mixture is then neutralized with 2 Nhydrochloric acid to a pH of 7 and then extracted 3 times with 200 ml.(each) of chloroform. The combined extracts are then dried overanhydrous sodium sulfate and then evaporated to dryness in vacuo toobtain 3 (p-carboxyethyl)-4-phenyl-1,2,3,4- tetrahydroquinazoline as alight yellow amorphous residue.

Step D: Preparation of 6-phenyl-l,3,4,5-tetrahydro-6H-l,5-methano-l,5-benzodiazocin-2-one.To a solution of 10 g. of3(B-carboxyethyl)-4-phenyl-l,2,3,4-tetrahydroquinazoline and 10 ml. oftriethylamine in ml. of dry dioxane, at 5-10 C., is added dropwisewithin 5 to 10 minutes, 3.9 g. of ethyl chlorocarbonate. The resultingsolution is stirred at room temperature for 30 minutes and thenevaporated to dryness in vacuo at 4050 C. The residue is dissolved in200 ml. of methylene chloride and the resulting solution extracted twicewith 100 ml. (each) of a saturated sodium bicarbonate solution. Theorganic phase is dried over anhydrous sodium sulfate and then evaporatedand the residue crystallized from ethyl acetate to obtain'6-phenyl-l,3,4,5--tetrahydro-6H-l,S-methano-l, S-benzodiazocin-Z-one,M.P. 197-198 C.

Step E: Preparation of 6-phenyl-3,4,5,6-tetrahydro-[l,5]benzodiazocin-2(lH)-one.-A solution of 15 g. of 6 phenyl l,3,4,5tetrahydro 6H-l,5-methano-1,5- methano-l,5-benzodiazocin-2-one in 2100ml. of water and 140 ml. of 2 N hydrochloric acid is allowed to stand atroom temperature for 40 minutes, then made slightly basic by theaddition of 300 ml. of 1 N sodium bicarbonate solution and thenextracted 3 times with 200 ml. (each) of methylene chloride. Thecombined extracts are then dried over anhydrous sodium sulfate, filteredand the filtrate evaporated to dryness in vacuo. The residue iscrystallized from ethyl acetate to obtain 6-phenyl-3,4,5,6-tetrahydro-[l,5]benzodiazocin-2(1H) one, M.P. 19l- 193 C.

Step F: Preparation of1-methyl-6-phenyl3,4,5,6-tetrahydro-[l,5]benzodiazocin-2(lH)-one.To asolution of 0.5 g. of 6-phenyl-3,4,5,6-tetrahydro-[l,5]benzodiazocin-2(lH)-one in 10 ml. of dimethylformamide is added mg. of sodiummethoxide. The resulting mixture is stirred for 10 minutes at roomtemperature and then cooled to 10 C. To the resulting cooled solution isadded, within 10 minutes, 0.3 ml. of methyl iodide and the resultingmixture is allowed to stand for 15 minutes at 20 C. and then evaporatedin vacuo at 60 C. The residue is added to a mixture of 20 ml. ofmethylene chloride and 10 ml. of 5% sodium bicarbonate solution. Theorganic phase is separated, dried over anhydrous sodium sulfate andevaporated. The residue is crystallized from diethyl ether to obtain1-methyl-6-phenyl-3,4,5,6-tetrahydro-[ 1,5 ]benzodiazocin-2-(1H)-one,M.P. -141 C.

Step G: Preparation of 1-methyl-6-phenyl-3,4-dihydro-[1,5]benzodiazocin-2(1H)-one.To a solution of 0.6 g. of 1 methyl 6phenyl-3,4,5, 6-tetrahydro-[1,5]benzo diazocin-2(1H)-one in 20 ml. ofdioxane is added 5 ml. of an aqueous potassium permanganate solution(5.27 g./100 ml.). The reaction mixture is allowed to stand at roomtemperature for 3 hours, then filtered and the filtrate evaporated todryness in vacuo. The residue is added to a mixture of 20 ml. ofmethylene chloride and 10 ml. of a saturated solution of sodiumchloride. The organic phase is separated, dried over anhydrous sodiumsulfate and evaporated in vacuo to obtain1-methyl-6-phenyl-3,4-dihydro-[1,5]benzodiazocin-2( 1H) -one.

What is claimed is:

1. A compound of the formula no III wherein R represents hydrogen, loweralkyl or di(lower)alkylamino(lower)alkyl. 2. A compound of claim 1 inwhich R is loweralkyl. 3. A compound of the formula HO III wherein Xrepresents hydrogen, chloro, or bromo.

4. The compound of claim 3 which is 8-chloro-6-phenyl-3,4-dihydro-[ 1,5benzodiazocin-2( 1H -one.

5. The compound of claim 1 which is8-chloro-1-methyl-6-phenyl-3,4-dihydro-[1,5]benzodiazocin-2( 1H) -ne.

6. The compound of claim 1 which is l-methyl-6-phenyl-3,4-dihydro- 1,5benzodiazocin-2( 1H -one.

7. A compound of the formula (1H)-one.

12. A compound of the formula Olin] X- wherein X represents hydrogen,chloro, bromo, nitro or trifluoromethyl.

13. The compound of claim 12 which is 8-chloro-6- phenyl 1,3,4,5tetrahydro 6H 1,5 methano 1,5- benzodiazocin-2-one.

14. The compound of claim 12 which is 6 phenyl- 1,3,4,5 tetrahydro 6H1,5-methano-1,5-benzodiazocin-2-0ne.

15. A process for preparing a compound of claim 1 wherein X is asdefined in claim 1 and R represents lower alkyl ordi(lower)alkylamino(lower)alkyl, which comprises contacting thecorresponding 6-phenyl-1,3,4,S-tetrahydro 6H 1,5 methano 1,5benzodiazocin 2- one with a strong acid, contacting the resultingproduct with an alkylating agent and oxidizing the resulting alkylatedproduct with permanganate ions.

16. A process for preparing a compound of claim 1 wherein X is asdefined in claim 1 and R represents lower alkyl ordi(lower)alkylamino(lower)alkyl, which comprises contatcing thecorresponding 6 phenyl 1,3,4,5- tetrahydro 6H 1,5methano-1,5-benzodiazocin-2-one with a strong acid, oxidizing theresulting product with permanganate ions and contacting the resultingoxidized product with an alkylating agent.

17. A process for preparing a compound of claim 1 wherein X is asdefined in claim 1 and R represents hydrogen, which comprises contactingthe corresponding 6- phenyl 1,3,4,5 tetrahydro6H-1,5-methano-1,5-benzodiazocin 2 one with a strong acid and oxidizingthe resulting product with permanganate ions.

18. A process for preparing a compound of claim 7 wherein X and R are asdefined in claim 5 which comprises oxidizing the corresponding6-phenyl-3,4,5,6-tetrahydro-[1,5]benzodiazocin-2(1H)-one withpermanganate 19. A process for preparing a6-pheny1-3,4,5,6-tetrahydro-[1,5]benzodiazocin-2(1H)-one which comprisescontacting the corresponding 6-phenyl-l,3,4,5-tetrahydro-6H-1,5-methano-1,5-benzodiazocin-2-one with astrong acid.

20. A process for preparing a 6-phenyl-3,4-dihydro-[1,5]benzodiazocin-2(1H)-one which comprises contacting thecorresponding 6 pheny1-3,4,5,6-tetrahydro-[1,5] benzodiazocin-2(lH)-onewith permanganate ions.

References Cited UNITED STATES PATENTS 3,294,782 12/ 1966 Sulkowski260-2393 3,299,053 l/ 1967 Archer et a1 260-2393 3,371,085 2/ 1968Reeder et al 260-2393 H'ENRY R. JILES, Primary Examiner R. T. BOND,Assistant Examiner U.S. Cl. X.R.

